Adeno-associated virus type 2 vectors: transduction and long-term expression in cerebellar Purkinje cells in vivo is mediated by the fibroblast growth factor receptor 1 : bFGFR-1 mediates AAV2 transduction of Purkinje cells.
The receptor for adeno-associated virus serotype 2 (AAV2) in Purkinje cells has not been identified, but based on work carried out in non-neuronal cell lines, heparan sulfate proteoglycan is thought to act as a primary receptor, with basic fibroblast growth factor receptor-1 being reported as a co-receptor. In this study, using antibody interference and protein competition strategies, we show specific reduction in Purkinje cell transduction by AAV2 vector in the presence of these inhibitors. We also demonstrate AAV2-mediated transgene expression in Purkinje cells in vivo that extends out to one year post-injection. These results provide new information on fibroblast growth factor receptor-1 involvement in AAV2-mediated transduction of Purkinje cells and have important implications for AAV-mediated treatment of various cerebellar disorders.
Belur
Lalitha R
LR
Gene Therapy Program, Institute of Human Genetics, University of Minnesota, Minneapolis, MN 55455, USA.
Kaemmerer
William F
WF
McIvor
R Scott
RS
Low
Walter C
WC
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000821:virology; D000229:Dependovirus / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics*; D051379:Mice; D011689:Purkinje Cells / Q000378:metabolism* / Q000821:virology; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics / Q000378:metabolism*; D014161:Transduction, Genetic
D051496:Receptor, Fibroblast Growth Factor, Type 1